Week 5 Flashcards
(48 cards)
Ligand-gated ion channels
a) Timescale
b) Effector
c) Coupling
d) Examples
a) milliseconds
b) channel
c) direct
d)
- nAChR
- GABAaR
- NMDAR
What are the 5 Cys loop LGIC receptors?
- Muscle nicotinic
- Neuronal nicotinic
- GABAa
- Glycine
- 5-HT
LGICs can be pentameric, tetrameric or trimeric. What specific types of receptor fit into each of these groups
Pentameric
- nAChR
- GABAa
- 5-HT3
Tetrameric
- NMDA
Trimeric
- P2XR
Describe the structure of nAChR:
How many subunits, how many transmembrane domains, TM2, any extra features
- Pentameric
- 4 Transmembrane domains
- TM2 lines the pore (-ive)
- Extracellularly located NH3+ and COO-
What are the 3 locations nAChRs are found?
- NMJ (endplate)
- Autonomic ganglia
- Synapses within the CNS
Key structural features of nAChRs:
All subunits contain approximately 500 amino acids. The homology between THE SAME subunit across species is a)__________ (b)________%). Whereas homology between different subunits in the same species is c)___________ (d)___________)
All subunits have Cys loops at 136/141
The ACh binding site is on the alpha-subunit
- 30-60%
- Low
- High
- 50-90%
a) High
b) 50-90%
c) Low
d) 30-60%
All subunits have a similar tertiary structure.
This is pretty complicated
A large a)__________ region and 4 b)__________ regions which are c)______________
A large d)____________ between TM3 and TM4 and extracellular e)________. f)_________ from each subunit lines the channel.
Subunits are all from separate genes.
- Intracellular Loop
- Extracellular
- Alpha Helices
- TM2
- Transmembrane
- NH2 and COOH
a) Extracellular
b) Transmembrane
c) Alpha helices
d) Intracellular
e) NH2 and COOH
f) TM2
The principle subunit of ACh binding is the alpha subunit. However, the gamma subunit is also important.
a)________ loops in the alpha subunit and b)_______ loops in the complementary gamma subunit form the binding site for ACh. Disruption to any of these loops interferes with ACh binding
- 2
- 6
- 3
- 4
a) 3
b) 3
Why is the Cys loop important in the nAChR? / What does it do?
It is important in the transduction of the signal when ACh binds
The GABAa receptor is formed from up to 20 different subunits. Most common though is what grouping of subunits?
Alpha and Beta subunits are usually together with gamma
Tough one, what is:
a) a selective GABAa receptor agonist
b) a selective, competitive GABAa antagonist
a) Muscimol
b) Bicuculine
GABAa receptors mediate a) fast/slow b) inhibitory/excitatory synaptic potentials
a) fast
b) inhibitory
The GABAa receptor is selectively permeable to Cl- ions. This means we can use the WHAT equation to determine where the synaptic potential reverses polarity?
Nernst Equation
Many clinically useful drugs act to block the interaction of ACh and the nicotinic AChR. These can be classified as either a) depolarising blockers or b) non-depolarising blockers. How are these things different and give an example of each?!
a) Depolarising blockers initially cause the depolarisation of the motor endplate leading to muscle contraction (fasciculation). Persistent receptor activation results in prolonged muscle paralysis
An example is Suxamethonium
b) Non-depolarising competitively block ACh without causing initial depolarisation. This leads to muscle relaxation. Non-depolarising blockers can be overcome by administration of an anti-cholinesterase drug (such as neostigmine)
Example drug = Rocuronium
In the parasympathetic nervous system, ACh activates WHAT kind of cholinergic receptor on the effector tissue after it is released from postganglionic nerve endings?
Muscarinic
There are 5 types of muscarinic receptor: M1-M5. What does each subtype do?
- M1: Neural
- M2: Cardiac
- M3: Secretion, contraction of visceral smooth muscle, vascular relaxation
- M4 + M5: Found in the CNS
Important one!
What are the effects of muscarinic receptor activation?
- Activate phospholipase C to cause production of IP[3] and diacyl glycerol
- Inhibit adenylate cyclase causing a decrease in levels of cAMP
- Activate K+ channels
- Inhibit Ca2+ channels
Some examples of direct acting agonists of muscarinic receptors are:
a) Bethanechol
b) Pilocarpine
What are these compounds?
a) Primarily muscarinic agonist, weak nicotinic agonist. Not hydrolysed by cholinesterase
b) Pilocarpine is an alkaloid also with primarily muscarinic effects. Crosses biological membranes
What are 2 therapeutic uses for muscarinic cholinomimetics and what drug(s) would be used to treat the conditions? Also add mechanisms.
1) Glaucoma
Drug = Pilocarpine
Mechanism: Underlying cause of glaucoma is problems with aqueous humor drainage. The resulting build up of pressure is painful. Contraction of the pupil and ciliary muscle by muscarinic receptor activation widens anterior angle of the eye and promotes drainage
2) Intestinal Atony (Lack of normal muscle activity in the gut)
Drugs: Bethanecol (direct acting, Neostigmine (indirect)
Mechanism: Muscarinic receptor activation increases gut movement and aids urination by working on gi muscles.
What are 2 competitive muscarinic antagonists that block all functions of muscarinic receptors? Hint = last Q is one of them
- Atropine
- Hyoscine: readily crosses into CNS
What are the pharmacological actions of Atropine in the following areas:
a) GI tract
b) Eye
c) Cardiovascular system
d) Urinary tract
e) Exocrine glands
f) Respiratory tract
g) CNS
a) Decreases GI motility
b) Causes pupil dilation due to blockage of cholinergic muscarinic receptors of pupil constrictor muscles
c) Causes tachycardia since the effects of vagal stimulation are blocked
d) Decreases bladder motor activity
e) Dry eyes, dry mouth and dry skin which can elevate body temperature
f) Causes bronchodilation and reduced mucus secretion
g) Produces mainly excitatory effects in the CNS. Low doses = restlessness, high doses = hallucinations and respiratory depression
Tough one but match the following drugs to their actions. They all affect something to do with ACh:
a) Synthesis of ACh
b) Storage of ACh
c) Release of ACh
- Botulinium toxin
- Vesamicol
- Hemicholinium
- Tetrodotoxin
a) Hemicholinium: Blocks transport of choline into the nerve terminal
b) Vesamicol: Transport of ACh to vesicles
c)
- Botulinium toxin: Prevents fusion of vesicles with presynaptic membrane
- Tetrodotoxin: blocks Na+ channels, preventing AP
In the parasympathetic nervous system, ACh activates a) (nicotinic/muscarinic) on effector tissues after it is released from the b) (preganglionic/postganglionic) nerve endings
a) Muscarinic
b) Postganglionic
What are the different classes of adrenoreceptors and their properties?
- alpha-1: Found post-junctionally; contraction of smooth muscle, relaxation of GI tract, vasoconstriction
- alpha-2: On nerve endings, reduce NA release
- beta-1: in heart, increase HR and force of contraction
- beta-2: in smooth muscle, relaxation and blood vessel dilation
- beta-3: on fat cells, stimulate lipolysis
